The Impact of Factor Xa Inhibition on Thrombosis, Platelet Activation, and Endothelial Function in Peripheral Artery Disease
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Endothelium-dependent, flow-mediated dilation (FMD) of the brachial artery
研究概览
简要总结
The purpose of this study is to understand how the drug rivaroxaban improves symptoms associated with peripheral artery disease.
详细描述
The Primary Investigator's central hypothesis is that activation of thrombotic pathways and downstream effectors of factor Xa signaling contribute to the development of PAD and its complications.
Aim 1: To assess the impact of rivaroxaban on macrovascular endothelial function in a randomized, double-blind, placebo-controlled crossover intervention in humans with PAD.
Aim 2: To assess the impact of rivaroxaban on PAR-1-mediated platelet activation in addition to its pleiotropic effects on thrombosis, thrombolysis, and inflammation in a randomized, double-blind, placebo-controlled crossover intervention in humans with PAD.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •History of peripheral artery disease (PAD) defined as:
- •Previous aorto-femoral bypass surgery, limb bypass surgery, or percutaneous transluminal angioplasty revascularization of the iliac or infra-inguinal arteries, or
- •Previous limb or foot amputation for arterial vascular disease, or
- •An ankle/arm blood pressure (BP) ratio less than 0.90, or
- •Significant peripheral artery stenosis (≥50%) documented by angiography, or by duplex ultrasound, or
- •An ankle-brachial index (ABI) greater than 1.4 with a toe-brachial index (TBI) less than 0.7 AND
- •Willing and able to provide written informed consent
- •Receiving aspirin therapy prior to enrollment
排除标准
- •High risk of bleeding
- •Stroke within 1 month of any history of hemorrhagic or lacunar stroke
- •Severe heart failure with known ejection fraction less than 30% or New York Heart Association (NYHA) class III or IV symptoms
- •Estimated glomerular filtration rate less than 15 mL/min/1.73m2
- •Need for dual-antiplatelet therapy, other non-aspirin antiplatelet therapy, or oral anticoagulant therapy
- •Known non-cardiovascular disease that is associated with poor prognosis (e.g. metastatic cancer) or that increases the risk of an adverse reaction to study interventions
- •History of hypersensitivity or known contraindication to rivaroxaban or aspirin
- •Systemic treatment with strong inhibitors of both CYP 3A4 and p-glycoprotein (e.g. systemic azole antimycotics, such as ketoconazole, and human immunodeficiency virus [HIV]-protease inhibitors, such as ritonavir), or strong inducers of CYP 3A4, i.e. rifampicin, rifabutin, phenobarbital, phenytoin, and carbamazepine
- •Any known hepatic disease associated with coagulopathy
- •Subjects who are pregnant, breastfeeding, or are of childbearing potential, and sexually active and not practicing an effective method of birth control (e.g. surgically sterile, prescription oral contraceptives, contraceptive injections, intrauterine device, double- barrier method, contraceptive patch, male partner sterilization)
- •Concomitant participation in another study with investigational drug
- •Upcoming invasive procedure within 3 months
- •Invasive procedure within the prior 1 month
- •Being treated for an active infection
- •Acute or chronic limb-threatening ischemia
- •Known contraindication to any study related procedures
研究组 & 干预措施
Control
Participants will receive 81mg daily of aspirin + placebo for 30 days.
干预措施: Aspirin 81Mg Ec Tab (Drug)
Control
Participants will receive 81mg daily of aspirin + placebo for 30 days.
干预措施: Placebo (Drug)
Intervention
Participants will receive 81mg of aspirin + rivaroxaban 2.5mg twice daily for 30 days.
干预措施: Rivaroxaban 2.5 Mg Oral Tablet (Drug)
Intervention
Participants will receive 81mg of aspirin + rivaroxaban 2.5mg twice daily for 30 days.
干预措施: Aspirin 81Mg Ec Tab (Drug)
结局指标
主要结局
Endothelium-dependent, flow-mediated dilation (FMD) of the brachial artery
时间窗: Baseline to 37 days
FMD will be measured by forearm high-resolution ultrasonography after treatment with low-dose rivaroxaban plus aspirin and compared to the baseline value following treatment with aspirin plus placebo.
Endogenous PAR-1 activation as measured by flow cytometry
时间窗: Baseline to 37 days
Endogenous PAR-1 activation, a novel marker of platelet activation, will be measured by flow cytometry, following treatment with low-dose rivaroxaban plus aspirin and compared to the baseline value following treatment with aspirin plus placebo. The unit of measure will be relative fluorescence.
次要结局
- Partial thromboplastin time(Baseline to 37 days)
- von Willebrand factor (vWF)(Baseline to 37 days)
- D-Dimer(Baseline to 37 days)
- Prothrombin time(Baseline to 37 days)
- High-sensitivity C-reactive protein.(Baseline to 37 days)
- Tumor necrosis factor-alpha(Baseline to 37 days)
- Interleukin-1beta(Baseline to 37 days)
- Interleukin-6(Baseline to 37 days)
- Soluble intercellular adhesion molecule-1 (slCAM-1)(Baseline to 37 days)
- Monocyte chemoattractant protein-1 (MCP-1)(Baseline to 37 days)
- Plasminogen activator inhibitor 1 (PAI-1)(Baseline to 37 days)
- CD41a (Integrin alpha-II-beta)(Baseline to 37 days)
- CD62p (P-Selectin)(Baseline to 37 days)
研究者
Aaron W. Aday, MD, MSc
Assistant Professor Division of Cardiovascular Medicine
Vanderbilt University Medical Center